Many of the adverse effects of cerebral dysfunction with age have been attributed to changes in metabolic function which presumably lead to a diminished capacity of aging tissue to sustain maximal physiological efficiency, particularly under conditions of high energy demand, i.e. stress-mediated situations. The proposed research projects are designed to determine to what extent neuronal function changes with age and whether known age-related changes in CNS function and related pathophysiological alterations are correlated with and/or mediated by age-related changes in brain bioenergetics and cerebral metabolism. Our approach includes a combination of physiological, biochemical, and pharmacological studies involving the development of non-traumatic optical techniques, i.e. microfluorometry and reflectance and transillumination spectrophotometry, to monitor intramitochondrial function and bioenergetic activities in the intact brain of young and aged animals. Without disturbing the integrity of the tissue, this approach will permit the rapid detection of differences in the reduction/oxidation (redox) states of components of the respiratory chain in-vivo; e.g. NAD/NADH and cytochromes, as well as changes in cerebral blood volume and oxygenation/disoxygenation states of hemoglobin. Such techniques, in combination with biochemical metabolite assay procedures, will provide a basis for evaluating cerebral oxidative metabolism during "resting" or non-stimulated conditions as well as during stress mediated states of brain activation by electrical stimulation and/or pharmacological induced alterations. Results from these studies will allow us to consider possible pharmacological management of difficulties arising from senile organic brain syndrome in the elderly.